Work

As2S2 restores erythroid maturation in sf3b1-deficient zebrafish by upregulating smad7

Year: 2026

Type: article

Abstract: SF3B1 is among the most frequently mutated genes in myelodysplastic syndromes (MDS) and is closely associated with aberrant erythropoiesis, yet strategies to restore terminal erythroid maturation in SF3B1-linked disease are limited. Using a zebrafish sf3b1 knockdown model, we demonstrate that arsenic disulfide (As₂S₂) reinstates erythroid reporter expression and hemoglobinization in morphants and yields partial persistence of rescue at later stages. Integrated transcriptomic and proteomic analyses show that As₂S₂ remodels metabolic and translational programs and attenuates TGF-β pathway activity, notably inducing the inhibitory mediator smad7. Comparative analysis with pharmacologic TGF-β inhibition reveals an overlapping therapeutic axis, validating a Smad7-dependent mechanism. These results identify As₂S₂ as an in vivo chemical probe that counteracts sf3b1-dependent erythroid failure via upregulation of Smad7 and highlight Smad7 as a candidate for therapeutic modulation in SF3B1-associated ineffective erythropoiesis.

Source: Annals of Hematology

DOI: 10.1007/s00277-026-07324-2